Various medical conditions, including but not limited to certain forms of cancer, hepatic malfunctions, dementias such as Alzheimer's disease, and various lipid abnormalities can be advantageously treated using inhibitors of HMG-CoA reductase. It is also posited that various other diseases and medical conditions are related to pathways that utilize HMG-CoA reductase. Thus treatment regimens utilizing HMG-CoA reductase inhibitors are valuable and warranted.
In many instances, combination therapies employing two or more therapeutic compounds are required to adequately address the medical condition and/or physical effects secondary to the condition under treatment. Thus, HMG-CoA reductase inhibitors can be employed with various other therapeutic agents to address lipid abnormalities. Combining two lipid-lowering medications safely and effectively improves overall beneficial effect on all lipid abnormalities and reduces multiple coronary heart disease risk factors.
Coronary heart disease (CHD) is currently managed by various drug therapies that include HMG-CoA reductase inhibitors (collectively known as statins), as well as other compounds such as fibrates, bile acid sequestrants, niacin and the like. Of these drugs, statins are the most prescribed because they are effective in lowering total cholesterol and low-density lipoprotein cholesterol (LDL-C). It has been found that statins have a small to moderate effect on triglycerides and a minimal effect at raising high-density lipoprotein cholesterol (HDL-C) levels, the so-called “good cholesterol”. While the National Cholesterol Education Program (NCEP) treatment guidelines recognize LDL-C as the primary target of therapy for prevention, it now focuses on HDL-C levels as a major risk factor. Moreover, the Adult Treatment Panel (ATP) of NCEP has now raised the HDL-C lower limit from 35 mg/dL to 40 mg/dL.
Statins are not effective at increasing HDL-C. However, various other materials such as fibrates can increase the level of HDL-C “good cholesterol.” Combined statin and fibrate therapy is often imperative for the improvement of the serum lipid profile in patients with mixed hyperlipidemia. However, the potential risk of myopathy has limited the widespread use of such therapy. Current combination therapies recommend separate dosing to minimize peak dose interactions. Thus, dosing regimens can include weekly administration of a material such as a fibrate together with daily statin treatment. Other treatment regimens may include a fibrate prescribed in the morning and a statin prescribed at night to minimize peak dose interactions. Such dosing complexity can lead to compliance problems and less than desirable dose response in a patient.
Thus, it would be desirable to develop formulations of water-soluble salts of statin dihydroxy open acid and other suitable components having suitable effect on cholesterol, triglyceride, or related blood chemistries. It would also be desirable to provide a formulation of such materials in a single pill or dose form in order to address the overall lipid abnormalities. It would also be desirable to provide a dose form in which the water-soluble statin dihydroxy acid salt and other lipid addressing materials are present in a form that would enable formulation of a combination drug that can be administered at therapeutically effective low doses in order to eliminate undesirable side effects.
Similar dosing complexities exist in treating other medical conditions for which HMG-CoA reductase inhibitors can be utilized. Thus, it would be desirable to provide therapeutic compositions that combine HMG-CoA reductase inhibitors and other complementary agents in a single dose form for treating various illnesses and conditions that are moderated or controlled by HMG-CoA reductase.